EP1058542A1 - Procede de preparation de grains granulaires spheriques enrobes - Google Patents

Procede de preparation de grains granulaires spheriques enrobes

Info

Publication number
EP1058542A1
EP1058542A1 EP99908932A EP99908932A EP1058542A1 EP 1058542 A1 EP1058542 A1 EP 1058542A1 EP 99908932 A EP99908932 A EP 99908932A EP 99908932 A EP99908932 A EP 99908932A EP 1058542 A1 EP1058542 A1 EP 1058542A1
Authority
EP
European Patent Office
Prior art keywords
pellets
polymer
active ingredient
coated
hours
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Granted
Application number
EP99908932A
Other languages
German (de)
English (en)
Other versions
EP1058542B1 (fr
Inventor
Torsten Wagner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Bayer Pharma AG
Original Assignee
Schering AG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Schering AG filed Critical Schering AG
Publication of EP1058542A1 publication Critical patent/EP1058542A1/fr
Application granted granted Critical
Publication of EP1058542B1 publication Critical patent/EP1058542B1/fr
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
    • A61K31/558—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes
    • A61K31/5585—Eicosanoids, e.g. leukotrienes or prostaglandins having heterocyclic rings containing oxygen as the only ring hetero atom, e.g. thromboxanes having five-membered rings containing oxygen as the only ring hetero atom, e.g. prostacyclin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5089—Processes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P39/00—General protective or antinoxious agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Definitions

  • the invention relates to a method for producing coated, spherical granules, in particular for compositions with prostane derivatives.
  • Prostan derivatives and their preparation are described in detail in EP 0 011 591 (filing date: October 18, 1979).
  • the prostane derivatives are compounds derived from prostacyclin (PGI 2 ). They contain a methyl group instead of the 9 - ether oxygen atom in prostacyclin. Prostan derivatives are used to treat various diseases, with the cardiovascular and thromboaggregation-inhibiting effects clearly in the foreground.
  • the use of prostane derivatives as medicaments is described in detail in European publication EP 0 011 591.
  • Publications EP 0 055 208, EP 0 099 538 and EP 0 119 949 list carbacyclin derivatives which have similar indications to the prostane derivatives mentioned above.
  • Further prostane derivatives are described in publication EP 0 084 856, which have been proposed for use in inhibiting platelet aggregation, lowering systemic blood pressure or treating gastric ulcers. Iloprost is the most important prostane derivative.
  • Diffusion pellets are the most important group of coated multiparticulate dosage forms.
  • Polymers have become extremely important as coating materials for oral prolonged-release drug forms.
  • the types of polymer used are primarily ethyl cellulose or poly (meth) acrylic acid esters.
  • the polymers can be used either as an organic solution or dispersed in the aqueous phase. As they are more environmentally friendly, safer and cheaper to handle, aqueous polymer dispersions are increasingly being used in industry.
  • the best-known trade names are Aquacoat ECD 30®, Surelease® or Eudragit® NE 30 D, RL 30 D and RS 30 D.
  • the coating suspensions used for the coating process contain additional additives that are required for manufacturing and application reasons and the properties of the film former participate.
  • iloprost orally is carried out in two main steps.
  • active ingredient-containing raw pellets are produced using an extrusion / spheronization process.
  • the raw pellets consist of 90% lactose and 10% Avicel PH 101 as auxiliaries and contain lloprost-ß-cyclodextrin clathrate as the active ingredient.
  • the content is 0.05 or 0.1 mg iloprost per 65 or 130 mg pellets [active ingredient content approx. 0.08% (w / w)].
  • the raw pellets are then coated with a coating suspension based on Eudragit NE 30 D and additives coated in a fluidized bed device.
  • the raw pellets were in principle in a fluidized bed device (WSG), type GPCG-3 (from Glatt)) or type Strea (from Aeromatic) on a laboratory scale (both top spraying processes) with the same coating suspension sprayed, which is still used today.
  • the resulting drug release profile (determination of the amount of drug released after, for example, 1, 2 and 3 hours) served as the target for the paint application, which was examined in the dissolution test according to USP, apparatus I (basket).
  • the pellets produced were used for the first kinetic and clinical studies.
  • a problem from the beginning was the fact that with this formulation the release of active substance slowed down somewhat over the storage period.
  • the first larger batches (production scale) were coated in the WSG Aeromatic MP4 (Aeromatic).
  • the spray application was carried out in a counter-current process (top spraying).
  • a spray nozzle was used to spray the pellets in the fluidized bed from above in the opposite direction to the supply air flow.
  • the Aeromatic MP4 75 kg of raw pellets containing active ingredients were sprayed with 16.5 kg of lacquer suspension.
  • the object is to offer a method for producing a shell for spherical granules, with which an active ingredient release profile can be obtained which is within the specification even after a long storage period.
  • the object is achieved by a process for producing coated, spherical granules (pellets), the process comprising the following steps: ⁇ ) in a fluidized bed or fluidized bed, active substance-containing raw pellets made from at least one active pharmaceutical ingredient and optionally pharmaceutically acceptable additives and / or carriers sprayed with a polymer dispersion and additives which are an ethyl cellulose and / or a poly (meth) acrylic acid ester
  • Polymer comprises, ß) a polymer dispersion with a polymer thickness in the range of 1 to
  • the active pharmaceutical ingredient is a prostane derivative.
  • a fluidized bed or fluidized bed in which the pellets are sprayed in a direct current process is preferred.
  • a direct current process is more preferred, in which the polymer dispersion (and added additives) is sprayed into the fluidized bed or fluidized bed from at least 1 or 2, preferably 12, nozzles.
  • the polymer comprises either ethyl cellulose or a poly (meth) acrylic acid ester as the polymer.
  • the thickness of the polymer applied is evenly distributed over the pellet.
  • the tolerances of the polymer thickness should advantageously only be ⁇ 30%, preferably ⁇ 20% and more preferably ⁇ 10%.
  • the pellets comprising prostane derivatives and pharmaceutical carriers and / or additives as the active ingredient.
  • Low-dose active ingredients such as steroids (active ingredient content less than 1%) are also preferred.
  • the active ingredient is 5- (E) - (1S, 5S, 6R) -7-hydroxy-6 [(E) - (3S, 4RS) -3-hydroxy-4-methyl-1-octen-6- inyl] bicyclo [3.3.0] octen-3-ylidene pentanoic acid and as an additive at least cyclodextrin
  • polymer is the poly (meth) acrylic acid ester, which is described in the European Pharmacopoeia, 3rd edition, 1997, Deutscher maschiner Verlag Stuttgart, Eschborn, on page 1516 to page 1517 under point 733. This reference becomes part of the application by citation.
  • EUDRAGIT NE 30 D The most preferred polymer is EUDRAGIT NE 30 D, which is described in the following publications:
  • K. LEHMANN and H U: PETEREIT (1988) Use of aqueous poly (meth) acrylate dispersions for the production of matrix tablets, (1988) Acta Pharma. Tech. Vol. 34 (4), pp 189 and K. LEHMANN et al. (1989) Internship in varnish coating.
  • the pellets comprise the active pharmaceutical ingredient and furthermore pharmaceutically acceptable carriers and additives.
  • Such carriers and additives are described in Remington's Pharmaceutical Science, 15 t ⁇ ed. Mack Publishing Company, Easton Pennsylvania (1980).
  • Cyclodextrin is more preferred as the carrier. Cyclodextrin is formed after starch has been broken down by Bacillus macerans or Bacillus circulans under the action of cyclodextrin glycosyltransferase.
  • the cyclodextrins consist of 6, 7 or 8 ⁇ -1-4-linked glucose units ( ⁇ -, ⁇ - and ⁇ -cyclodextrins).
  • the cyclohexa- (hepta-, octa-) amyloses are layered on top of one another in the crystal lattice of the cyclodextrins in such a way that they form continuous internal molecular channels in which they can include hydrophobic molecules in varying amounts. (Literature: Adv.
  • the active pharmaceutical ingredient relates to prostane derivatives of the general formula I or II
  • X2 is a straight-chain or branched saturated alkylene group with 1 to 6
  • X3 is an -O- or -CH2-
  • X4 is -CH2- or - [CH2] 3-, X5 is -H or -C ⁇ C-R2;
  • R-1 is a hydrogen atom, an alkyl group with 1 to 6 carbon atoms, a cycloalkyl group with 5 or 6 carbon atoms or
  • R3 is a hydrogen atom, an acyl radical with 1 to 4 carbon atoms or a benzoyl radical and
  • R4 is -H or -CH3; where the -O-R3 group is a- or b-, and their salts with physiologically compatible bases, if R1 has the meaning of a hydrogen atom.
  • EP 0 011 591, EP 0 055 208, EP 0 099 538, EP 0 119 949, EP 0 084 856 and EP 0 686 036 describe the prostane derivatives, their preparation and use.
  • the publications are part of the disclosure with regard to the substances, their production and use.
  • Inorganic and organic bases are suitable for salt formation with the free acids.
  • examples include: alkali metal hydroxides such as sodium and
  • Potassium hydroxide alkaline earth metal hydroxides, such as calcium hydroxide, ammonia, amines, such as ethanolamine, diethanolamine, triethanolamine, N-methylglucamine, morpholine,
  • the ⁇ -cyclodextrin clathrates are produced in accordance with EP 0 259 468.
  • X2 is a straight-chain or branched saturated alkylene group with 2 to 4
  • X3 is a -CH2-
  • X4 is a -CH2-, X5 is a -C ⁇ C-R2;
  • Rl is a hydrogen atom, an alkyl group with 1 to 3 carbon atoms or phenylene group
  • R2 is a straight or branched chain, saturated or unsaturated alkyl group with 1 to 3 carbon atoms
  • R3 is a hydrogen atom or an acyl radical with 2 carbon atoms and
  • R4 is -H; where the -O-R3 group is a- or b-, and their salts with physiologically compatible bases, if R1 has the meaning of a hydrogen atom.
  • Iloprost a prostane derivative which has the systematic designation 5- (E) - (1 S, 5S, 6R) -7-hydroxy-6 [(E) - (3S, 4RS) -3-hydroxy-4-methyl-1-octen-6-ynyl] bicyclo [3.3.0] octen-3-ylidene pentanoic acid.
  • the active substance also includes cicaprost, eptaioprost, ciprosten and / or beraprost and their salts.
  • Active pharmaceutical ingredients can also be present as low-dose active ingredients, these are active ingredient contents of 1% and less (w / w) based on the total mass of active ingredient and carrier and additive. A percentage of 0.3 and less is preferred; more preferably 0.1 and less.
  • the lower temperature limit is 45 ° C., more preferably 47 ° C., even more preferably 48 ° C. and most preferably 50 ° C.
  • the upper temperature limit is preferably 65 ° C., more preferably 60 ° C., even more preferably 47 ° C. and most preferably 53 ° C. 10
  • the dwell time for tempering is at least 24 hours. Comparably good results are achieved by prolonged annealing. Poorer data for the drug release profile can be achieved by shortening it. A high temperature can usually affect the stability of the product. For this reason, the shortest possible times and gentle tempering conditions are desirable. A dwell time of 48 h ⁇ 5 h is most preferred.
  • Example 1 (old process, top spraying, production scale, no tempering)
  • Raw pellets containing active ingredient are produced by an extrusion / spheronization process.
  • an active ingredient / active ingredient premix (90% lactose, 90% ⁇ 0.1 mm, 10% Avicel PH 101 and lloprost- ⁇ -cyclodextrin clathrate) is granulated with water in a mixer.
  • the moist powder mixture is formed into a strand-like granulate through the perforated disc of an extruder, which is rounded in the spheronizer cell to spherical granules (pellets).
  • the raw pellets are then dried in a fluidized bed dryer.
  • Spray nozzle a two-substance nozzle, diameter 1.8 mm
  • the sustained release pellets thus obtained have the following composition:
  • Example 2 (old method, top spraying, laboratory scale, untempered and annealed at 50 ° C / 4 hours)
  • Spray nozzle a two-substance nozzle, diameter 1.0 mm
  • part of the sustained-release pellets are annealed at 50 ° C in a circulating air oven for 4 hours.
  • the sustained release pellets thus obtained have the following composition:
  • Example 3 modified, new process, bottom spraying, production scale, tempering at 50 ° C / 4 hours
  • Spray nozzle 12 three-substance nozzles, diameter 0.8 mm
  • part of the sustained-release pellets are annealed at 50 ° C in a circulating air oven for 4 hours.
  • the sustained release pellets thus obtained have the following composition:
  • Example 3 The storage took place at room temperature. As in Example 3, the product tempered at 50 ° C for 4 h shows a decrease in the release rates over a storage period of 4 weeks. The product is also not stable.
  • Example 4 new process / final process, bottom spraying, production scale, untempered and tempering at 50 ° C / 48 hours
  • Spray nozzle 12 three-substance nozzles, diameter 0.8 mm
  • the sustained-release pellets are annealed at 50 ° C in a circulating air oven for 48 hours.
  • the sustained release pellets thus obtained have the following composition: 0.050 mg iloprost
  • the storage took place at room temperature.
  • the product tempered at 50 ° C for 48 h, is stable even after a storage period of 9 months.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Epidemiology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Urology & Nephrology (AREA)
  • Cardiology (AREA)
  • Vascular Medicine (AREA)
  • Hematology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Toxicology (AREA)
  • Diabetes (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Glanulating (AREA)
  • Processing And Handling Of Plastics And Other Materials For Molding In General (AREA)
  • Processes Of Treating Macromolecular Substances (AREA)
  • Jellies, Jams, And Syrups (AREA)
  • Steroid Compounds (AREA)
  • Manufacturing Of Micro-Capsules (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

L'invention concerne un procédé de préparation de grains granulaires sphériques (pellets) dont l'enrobage est un polymère, notamment de la cellulose d'éthyle ou un ester d'acide poly(méth)acrylique et présente au moins les propriétés suivantes: a) le polymère a une épaisseur comprise entre 1 et 5 % (w/w) de la masse globale qui correspond à la composition du pellet enrobé; b) la pénétration du polymère est conçue de manière à intervenir pendant un recuit à une température comprise entre 45 et 65 DEG C; et c) la pénétration du polymère est conçue de manière à intervenir pendant un recuit durant au moins 24 heures; et epsilon ) le principe actif pharmaceutique est un dérivé de prostane. Le principe actif préféré est un acide 5-(E)-(1S,5S,6R)-7-hydroxy-6[(E)-(3S,4RS)-3-hydroxy-4-méthyle-1-octène-6-inyle]bicyclo [3.3.0]ctène-3-ylidènepentanique avec de la cyclodextrine comme additif.
EP99908932A 1998-02-24 1999-02-24 Procede de preparation de grains granulaires spheriques enrobes contenant des derivees du prostan Expired - Lifetime EP1058542B1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE19808634A DE19808634A1 (de) 1998-02-24 1998-02-24 Mantel für eine pharmazeutische Zusammensetzung
DE19808634 1998-02-24
PCT/EP1999/001100 WO1999043303A1 (fr) 1998-02-24 1999-02-24 Procede de preparation de grains granulaires spheriques enrobes

Publications (2)

Publication Number Publication Date
EP1058542A1 true EP1058542A1 (fr) 2000-12-13
EP1058542B1 EP1058542B1 (fr) 2005-08-31

Family

ID=7859315

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99908932A Expired - Lifetime EP1058542B1 (fr) 1998-02-24 1999-02-24 Procede de preparation de grains granulaires spheriques enrobes contenant des derivees du prostan

Country Status (18)

Country Link
US (1) US6723372B1 (fr)
EP (1) EP1058542B1 (fr)
JP (1) JP2002504506A (fr)
KR (1) KR100623542B1 (fr)
AT (1) ATE303133T1 (fr)
AU (1) AU753261B2 (fr)
CA (1) CA2321969C (fr)
CZ (1) CZ299252B6 (fr)
DE (2) DE19808634A1 (fr)
DK (1) DK1058542T3 (fr)
ES (1) ES2247786T3 (fr)
HU (1) HU226066B1 (fr)
IL (1) IL137965A (fr)
NO (1) NO20004225L (fr)
PL (1) PL193071B1 (fr)
RU (1) RU2209060C2 (fr)
SK (1) SK284062B6 (fr)
WO (1) WO1999043303A1 (fr)

Families Citing this family (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19828881A1 (de) 1998-06-22 1999-12-23 Schering Ag Oxidationsinhibitor bei Prostan-Derivaten
US8323692B2 (en) * 2002-02-21 2012-12-04 Valeant International Bermuda Controlled release dosage forms
ES2272914T3 (es) * 2003-05-20 2007-05-01 Ethypharm Composicion farmaceutica oral de liberacion sostenida.
US8318230B2 (en) * 2005-05-02 2012-11-27 Henkel Ag & Co. Kgaa Use of debranched starch in extrusion-spheronization pharmaceutical pellets
WO2007063946A1 (fr) 2005-11-30 2007-06-07 Fujifilm Ri Pharma Co., Ltd. Diagnostic et remede pour une maladie provoquee par l’aggregation et/ou le depot d’amyloide
RU2702690C2 (ru) * 2015-08-13 2019-10-09 БИОЛИНГУС АйПи ЛЛСи Способ получения продуктов, содержащих стабилизированные активные вещества, и композиций, содержащих таковые
CN106822013B (zh) * 2015-11-30 2020-05-12 北京泰德制药股份有限公司 前列环素类似物缓释制剂

Family Cites Families (14)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA935093A (en) * 1969-07-28 1973-10-09 Eurand S.R.L. Method of preparing granules with controlled release of the active substance contained therein
DE3608088C2 (de) * 1986-03-07 1995-11-16 Schering Ag Pharmazeutische Präparate, enthaltend Cyclodextrinclathrate von Carbacyclinderivaten
US5286494A (en) * 1986-07-02 1994-02-15 Schering Aktiengesellschaft Medicinal agents with sustained action
DE3622487A1 (de) * 1986-07-02 1988-01-14 Schering Ag Arzneimittel mit verzoegerter wirkstoffabgabe
IT1227899B (it) * 1988-12-23 1991-05-14 Poli Ind Chimica Spa Rivestimento totale o parziale di principi attivi farmaceutici e relative composizioni
US5286493A (en) * 1992-01-27 1994-02-15 Euroceltique, S.A. Stabilized controlled release formulations having acrylic polymer coating
JP3277342B2 (ja) * 1992-09-02 2002-04-22 武田薬品工業株式会社 徐放性マイクロカプセルの製造法
PH30929A (en) * 1992-09-03 1997-12-23 Janssen Pharmaceutica Nv Beads having a core coated with an antifungal and a polymer.
DE4236025A1 (de) * 1992-10-24 1994-04-28 Merck Patent Gmbh Orale Arzneiformen
US5376384A (en) * 1992-12-23 1994-12-27 Kinaform Technology, Inc. Delayed, sustained-release pharmaceutical preparation
FI94926C (fi) * 1993-11-12 1995-11-27 Leiras Oy Menetelmä klodronaattivalmisteen valmistamiseksi
US5958458A (en) * 1994-06-15 1999-09-28 Dumex-Alpharma A/S Pharmaceutical multiple unit particulate formulation in the form of coated cores
RU2117475C1 (ru) * 1995-11-02 1998-08-20 Химико-фармацевтическое акционерное общество открытого типа "Октябрь" Водная акриловая дисперсия для производства энтеральных лекарственных форм
JPH10139659A (ja) * 1996-09-10 1998-05-26 Freunt Ind Co Ltd 球形粒子群、その製造方法及びそれを用いた球形粒子製剤

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9943303A1 *

Also Published As

Publication number Publication date
DE59912501D1 (de) 2005-10-06
NO20004225L (no) 2000-09-28
HU226066B1 (en) 2008-04-28
CA2321969A1 (fr) 1999-09-02
AU2835299A (en) 1999-09-15
ES2247786T3 (es) 2006-03-01
CA2321969C (fr) 2007-04-10
IL137965A (en) 2005-11-20
JP2002504506A (ja) 2002-02-12
HUP0100752A2 (hu) 2001-08-28
KR20010041210A (ko) 2001-05-15
SK12422000A3 (sk) 2001-04-09
KR100623542B1 (ko) 2006-09-13
CZ20003088A3 (cs) 2000-11-15
WO1999043303A1 (fr) 1999-09-02
EP1058542B1 (fr) 2005-08-31
US6723372B1 (en) 2004-04-20
CZ299252B6 (cs) 2008-05-28
SK284062B6 (sk) 2004-09-08
NO20004225D0 (no) 2000-08-23
AU753261B2 (en) 2002-10-10
PL342315A1 (en) 2001-06-04
RU2209060C2 (ru) 2003-07-27
IL137965A0 (en) 2001-10-31
DK1058542T3 (da) 2006-01-02
PL193071B1 (pl) 2007-01-31
DE19808634A1 (de) 1999-08-26
ATE303133T1 (de) 2005-09-15

Similar Documents

Publication Publication Date Title
DE69636177T2 (de) Umhüllung kleiner Partikel
DE69520711T2 (de) Duloxetin enthaltende darmlösliche Pellets
DE69003568T2 (de) Arzneimittel mit verzögerter Freigabe.
EP0368216B1 (fr) Forme pharmaceutique solide à action retardée
EP0208971B1 (fr) Formes galéniques solides pour application orale contenant de la 9-déoxo-11-déoxy-9,11-(imino(2-(2-méthoxyéthoxy)éthylidène)-oxy-)-(9S)-érythromycine et leur procédé de préparation
DE19823940B4 (de) Enterische Fluoxetinpellets
EP0078430B1 (fr) Procédé de fabrication de préparations pharmaceutiques solides à libération rapide de dihydropyridines
DE60108255T2 (de) Clarithromycin enthaltende zubereitung mit verlängerter freisetzung
DE69222043T2 (de) Herstellungsverfahren von medikamentöse substanzen in granulatform
DE3915150C2 (de) Lang-wirkendes Diclofenac-Natrium-Präparat
DE19901692C2 (de) Verfahren zur Herstellung von Pellets mit einem Gehalt von bis zu 90 Gew.% eines pharmazeutischen Wirkstoffes
EP0181515A2 (fr) Procédé pour la préparation d'une dispersion aqueuse d'un produit d'enrobage et son utilisation pour enrober des compositions pharmaceutiques
AT6311U1 (de) Pharmazeutische zusammensetzung mit magensaftresistentem überzug und methode zur herstellung
DE2246037B2 (de) Peroral anwendbares Arzneimittel mit verzögerter Resorbierbarkeit in Suspensionsform
DE69625813T2 (de) Pranlukast enthaltende granula, verfahren zur herstellung der granula und verfahren zur verminderung des zusammenbackens von pranlukast
DE602005006409T2 (de) Ein amin-arzneimittel enthaltende granulatzubereitung mit langsamer freisetzung auf basis von teilchen mit einer überzugsschicht und entsprechendes herstellungsverfahren
DE60022332T2 (de) Ketoprofen- mikrogranulat, verfahren zur herstellung desselben sowie pharmazeutsche zusammensetzungen
EP1058542B1 (fr) Procede de preparation de grains granulaires spheriques enrobes contenant des derivees du prostan
DE69001682T2 (de) Wasserdisperierbare gemfibrozilhaltige mittel.
EP0285871B1 (fr) Granule à libération prolongée ne contenant pas d'agent liant
EP0116358B1 (fr) Complexes de prostaglandines
DE69311394T2 (de) Arzneimittel verzögerter Wirkstoffabgabe
DD200347A5 (de) Verfahren zur herstellung eines umhuellten acetylsalicylsaeurepraeparates
DE1467919C (de) Verwendung des Aluminiumsalzes der O-Acetylsalicylsäure in festen Arzneizubereitungsformen mit Depot-Wirkung
DE60312635T2 (de) Zusammensetzung in Form einer festen Dispersion enthaltend Itraconazol und ein hydrophilisches Polymer mit einer verbesserten Bioverfügbarkeit

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20000810

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

17Q First examination report despatched

Effective date: 20031105

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

RTI1 Title (correction)

Free format text: METHOD FOR PRODUCING ENCASED SPHERICAL GRANULAR GRAINS COMPRISING PROSTANE DERIVATIVES

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

Free format text: NOT ENGLISH

Ref country code: CH

Ref legal event code: EP

REG Reference to a national code

Ref country code: IE

Ref legal event code: FG4D

Free format text: LANGUAGE OF EP DOCUMENT: GERMAN

REF Corresponds to:

Ref document number: 59912501

Country of ref document: DE

Date of ref document: 20051006

Kind code of ref document: P

GBT Gb: translation of ep patent filed (gb section 77(6)(a)/1977)

Effective date: 20050920

REG Reference to a national code

Ref country code: SE

Ref legal event code: TRGR

REG Reference to a national code

Ref country code: DK

Ref legal event code: T3

REG Reference to a national code

Ref country code: GR

Ref legal event code: EP

Ref document number: 20050403626

Country of ref document: GR

REG Reference to a national code

Ref country code: ES

Ref legal event code: FG2A

Ref document number: 2247786

Country of ref document: ES

Kind code of ref document: T3

ET Fr: translation filed
PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20060601

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: PT

Payment date: 20100217

Year of fee payment: 12

Ref country code: MC

Payment date: 20100212

Year of fee payment: 12

Ref country code: LU

Payment date: 20100225

Year of fee payment: 12

Ref country code: IE

Payment date: 20100219

Year of fee payment: 12

Ref country code: ES

Payment date: 20100224

Year of fee payment: 12

Ref country code: DK

Payment date: 20100210

Year of fee payment: 12

Ref country code: CH

Payment date: 20100223

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: IT

Payment date: 20100225

Year of fee payment: 12

Ref country code: FR

Payment date: 20100226

Year of fee payment: 12

Ref country code: FI

Payment date: 20100215

Year of fee payment: 12

Ref country code: CY

Payment date: 20100204

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20100218

Year of fee payment: 12

Ref country code: DE

Payment date: 20100219

Year of fee payment: 12

Ref country code: AT

Payment date: 20100212

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: NL

Payment date: 20100215

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: BE

Payment date: 20100401

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: SE

Payment date: 20100212

Year of fee payment: 12

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GR

Payment date: 20100219

Year of fee payment: 12

BERE Be: lapsed

Owner name: *SCHERING A.G.

Effective date: 20110228

REG Reference to a national code

Ref country code: PT

Ref legal event code: MM4A

Free format text: LAPSE DUE TO NON-PAYMENT OF FEES

Effective date: 20110824

REG Reference to a national code

Ref country code: NL

Ref legal event code: V1

Effective date: 20110901

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: MC

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110228

REG Reference to a national code

Ref country code: CH

Ref legal event code: PL

REG Reference to a national code

Ref country code: DK

Ref legal event code: EBP

REG Reference to a national code

Ref country code: SE

Ref legal event code: EUG

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20110224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: PT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110824

Ref country code: LI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110228

Ref country code: CH

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110228

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20111102

REG Reference to a national code

Ref country code: IE

Ref legal event code: MM4A

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: BE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110228

Ref country code: GR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110902

Ref country code: FI

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

Ref country code: CY

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

Ref country code: AT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

Ref country code: NL

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110901

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 59912501

Country of ref document: DE

Effective date: 20110901

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110228

Ref country code: IE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

REG Reference to a national code

Ref country code: ES

Ref legal event code: FD2A

Effective date: 20120411

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: ES

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110225

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: SE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110225

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: LU

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110224

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20110901